The CRISPR-Cas system initiated a revolution in genome editing when it was, for the first time, demonstrated success in the mammalian cells. Today, scientists are able to readily edit genomes, regulate gene transcription, engineer posttranscriptional events, and image nucleic acids using CRISPR-Cas-based tools. However, to efficiently transport CRISPR-Cas into target tissues/cells remains challenging due to many extra- and intra-cellular barriers, therefore largely limiting the applications of CRISPR-based therapeutics in vivo. In this review, we summarize the features of plasmid-, RNA- and ribonucleoprotein (RNP)-based CRISPR-Cas therapeutics. Then, we survey the current in vivo delivery systems. We specify the requirements for efficient in vivo delivery in clinical settings, and highlight both efficiency and safety for different CRISPR-Cas tools.

中文翻译：

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体内 CRISPR-Cas 递送系统的合理设计。

当 CRISPR-Cas 系统首次在哺乳动物细胞中取得成功时，它引发了基因组编辑的革命。今天，科学家们能够使用基于 CRISPR-Cas 的工具轻松编辑基因组、调节基因转录、设计转录后事件和成像核酸。然而，由于存在许多细胞外和细胞内障碍，将 CRISPR-Cas 有效地转运到靶组织/细胞中仍然具有挑战性，因此在很大程度上限制了基于 CRISPR 的疗法在体内的应用。在这篇综述中，我们总结了基于质粒、RNA 和核糖核蛋白 (RNP) 的 CRISPR-Cas 疗法的特点。然后，我们调查了当前的体内递送系统。我们指定了临床环境中有效体内递送的要求，并强调了不同 CRISPR-Cas 工具的效率和安全性。